Fetuses are not subject to immune rejection as are other tissue grafts. These studies will examine alterations in the control of maternal immune responses sufficient to account for the apparent protection of the fetus in order to determine whether impairment of specific reactions occurs that is sufficient to allow in vivo maintenance of allogeneic tissues. The influence of pregnancy on sensitivity to antigenic stimulation, and the kinetics and magnitude of responses to T-independent and T-dependent antigens and mitogens will be characterized by quantitation of the plaque-forming cell and hemagglutination responses after primary immunization. The influence of pregnancy on the induction and recall of immunologic memory will be studied. We propose to explore the competence of T cell effector mechanisms relevant to tissue antigen recognition and destruction by observing the rate of foreign skin graft rejection, quantitating the delayed hypersensitivity response to contact sensitizing agents, and studying the ability of pregnant animals to induce and support a graft-versus-host response. Experiments will also examine the hypothesis that fetal lymphohematopoietic elements are capable of controlling maternal lymphocytes that enter the uterine sphere of influence, thereby eliminating the possibility of in vivo fetal rejection. This hypothesis will be tested by observation of the influence of fetal lymphocytes on lymphoproliferative responses of adult cells in well-characterized in vitro assay systems. If it is observed that the magnitude or kinetics of the responses is altered as consequence of exposure to fetal cells, the requirements for the regulation mechanisms of fetal cells will be explored in depth.